5-HT-moduline controls serotonergic activity: implication in neuroimmune reciprocal regulation mechanisms

The serotonergic neurotransmission is known as a neuromodulatory system exe rting its activity in the central nervous system (CNS) as well as at the pe riphery. The anatomical and morphological organization of the system based on a marked centralization of the cellular bodies and the large, almost ubi quitary, presence of axonal projections of the neurons is in good agreement with this modulatory role. Furthermore, a very high number of varicosities located along the axonal branches are capable of releasing serotonin (5-HT ). The amine stimulates a number of different specific receptor types which al lows 5-HT to exert different activities on its various cellular targets. Am ong these receptors, the 5-HT1B subtypes play a particular role as they are autoreceptors located on 5-HT neurons terminals and heteroreceptors locate d on non-serotonergic terminals where they control the release of the neuro transmitter. 5-HT-moduline, an endogenous tetrapeptide, regulates the efficacy of these 5-HT1B receptors, hence, is able to control the serotonergic activity in a synchronous manner for the various varicosities from a single neuron and th us may favour the differential effect of that neuron on distinct cerebral f unctions. Accordingly, the peptide allows the 'fine tuning' of the cerebral activity by the serotonergic system to elaborate the response given by the brain to a particular stimulus, that is, stress situations. At the periphery, the serotonergic system also appears to possess a regulat ory activity via 5-HT1B receptors. In particular, the receptors located on immunocompetent cells control their activity and are themselves regulated b y 5-HT-moduline likely originating from adrenal medulla and released after acute stress. The serotonergic system appears to play a major role in the reciprocal sign alling existing between the neuronal and the immune system. The participati on of 5-HT-moduline is likely in physiological functions as well as in path ological disorders affecting central and peripheral activities. (C) 1999 El sevier Science Ltd. All rights reserved.